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ORIGINAL ARTICLE
Year : 2022 | Volume
: 23
| Issue : 2 | Page : 98-104
A prospective randomized study to compare intrathecal isobaric levobupivacaine with or without fentanyl in various infraumbilical surgeries
Veena Mathur, Anand Kumar Verma, Arvind Khare, Deepak Kumar Garg, Beena Thada, Maina Singh
Department of Anaesthesiology, J. L. N. Medical College, Ajmer, Rajasthan, India
Correspondence Address:
Dr. Deepak Kumar Garg
New OT, Department of Anaesthesiology, J.L.N. Hospital, Ajmer- 305001, Rajasthan
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/TheIAForum.TheIAForum_2_22
Background and Aims: Subarachnoid block is the most preferred anesthetic technique for infraumbilical surgeries as it provides better postoperative analgesia, effective muscle relaxation, and cost-effectiveness. Levobupivacaine is preferable over bupivacaine due to its lower cardiotoxicity, prolonged sensory block, and shorter duration of motor block. Opioids as an adjuvant to intrathecal local anesthetics enhance the quality of both analgesia and anesthesia during intraoperative as well as postoperative period. The present study aimed to compare levobupivacaine with and without fentanyl in spinal anesthesia.
Methods: In this prospective, randomized, double-blinded study, a total of 80 patients belonging to the American Society of Anesthesiologists Physical Status I and II were enrolled for infraumbilical surgeries. Patients were randomly allocated into two groups. Group Levobupivacaine (L) (n = 40) received isobaric levobupivacaine 0.5% 2.5 ml with 0.5 ml normal saline and Group Levobupivacaine + fentanyl (LF) (n = 40) received isobaric levobupivacaine 0.5% 2.5 ml with fentanyl 25 μg (0.5 ml). Time of onset and duration of both sensory and motor block, Visual Analog Scale score, duration of analgesia, hemodynamic changes, and any adverse events were noted in both the groups.
Results: The onset of both sensory and motor block was significantly faster in Group LF (P < 0.05). The duration of sensory block was significantly longer in Group LF (P < 0.05). The duration of motor block was found to be comparable between two groups with stable hemodynamics and no perioperative sedation (P > 0.05). The duration of analgesia was significantly longer in Group LF (336.5 ± 31.3 min) compared to Group L (223.65 ± 32.17 min) P < 0.001.
Conclusion: Intrathecal fentanyl (25 μg) can be effectively used as an adjuvant to isobaric 0.5% levobupivacaine as it provides better block characteristics with minimal adverse effects in patients undergoing infraumbilical surgeries.
Keywords: Fentanyl, infraumbilical surgeries, levobupivacaine, spinal anesthesia
Spinal anesthesia is almost the most preferred anesthetic technique for infraumbilical surgeries due to its better reliability and cost-effectiveness along with good muscle relaxation, intraoperative and postoperative analgesia. Nowadays, more and more surgeries are performed as day-care surgeries.[1] In routine, 0.5% hyperbaric bupivacaine is used in spinal anesthesia for infraumbilical surgeries. However, bupivacaine may cause hemodynamic instability, delayed regression of motor effect, and cardiac toxicity. Levobupivacaine, an amino-amide local anesthetic drug, S-enantiomer of bupivacaine which produces a differential neuraxial blockade has a faster onset of both sensory and motor block with prolonged duration of sensory block and lower cardiac toxicity.[2]
Postoperative analgesia is of great concern even after having knowledge of physiology of acute pain, the development of newer opioid and nonopioid analgesics, use of different methods and routes of drug delivery, and more widespread use of minimally invasive surgical techniques.[3] Various intrathecal adjuvants have been used to improve the quality of analgesia and anesthesia that also reduced the adverse effects associated with higher doses of local anesthetic alone.[4] The combination of local anesthetics and opioids administered intrathecally was reported to have a synergistic effect in terms of prolonging the duration of sensory block and analgesia without prolonging motor block.[5] Hence, many additives such as fentanyl and sufentanil have been administered along with local anesthetics to enhance the duration of sensory block without intensifying the motor block.
We hypothesized that intrathecal fentanyl used as an adjuvant with isobaric levobupivacaine would enhance the duration of analgesia and sensory block without prolonging motor block, so the present study was undertaken to compare the various characteristics of subarachnoid block, total rescue analgesic requirement, and hemodynamic changes following the administration of intrathecal 25 μg fentanyl combined with 0.5% isobaric levobupivacaine (12.5 mg) versus similar dose of local anesthetic without adjuvant in patients undergoing infraumbilical surgeries. The present study was conducted to evaluate the duration of analgesia as the primary objective while onset and duration of sensory block, onset and duration of motor block, perioperative sedation score, hemodynamic changes (perioperative as well as postoperative), and adverse effects/complications as secondary objectives.
MethodsAfter obtaining Institutional Ethics Committee Approval (979/Acad-III/MCA/2019 dated May 15, 2019) and registration in Clinical Trial Registry-India (CTRI/2019/12/022353 dated December 13, 2019), 80 patients aged 18–65 years of either sex belonging to the American Society of Anesthesiologists Physical Status I or II and posted for various infraumbilical surgeries were included in this prospective, randomized, double-blinded study. Patients with known hypersensitivity to study drugs, i.e., local anesthetics or opioids, and patients with any contraindication for the subarachnoid block were excluded from this study.
The sealed envelope technique was used for randomization of the patients, in which each preparation was sealed in an individual envelope, followed by shuffling of all envelopes. The study drug was diluted up to a total volume of 3.0 ml. Patients received either 12.5 mg of levobupivacaine or levobupivacaine 12.5 mg plus fentanyl 25 μg. To ensure blinding, the study solutions were prepared by a resident anesthesiologist who was not involved in the study thereafter [Figure 1].
All patients underwent preanesthetic evaluation the day before surgery and were kept nil per oral as per the institute protocol. After arrival of the patient in the operating room, baseline vital parameters which included heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO2), and respiratory rate (RR) were noted, followed by preloading with ringer's lactate at 10 ml/kg. Under all aseptic precautions, spinal anesthesia was administered in a sitting position using a 25G Quincke needle at the L2–L3 or L3–L4 interspace. Patients in Group A received injection 0.5% isobaric levobupivacaine 2.5 ml (12.5 mg) with injection normal saline 0.5 ml, while patients in Group B received injection 0.5% isobaric levobupivacaine 2.5 ml (12.5 mg) isobaric with injection fentanyl 0.5 ml (25 μg).
Vital parameters including HR, SBP, DBP, mean arterial pressure (MAP), SpO2, and RR were monitored every 2 min till 10 min, then every 5 min till 30 min, and every 15 min till the end of the surgery. Bradycardia and hypotension were treated when HR <60 beats/min and MAP <60 mmHg and managed with an intravenous (IV) bolus of atropine 0.6 mg and ephedrine 6 mg with IV fluids, respectively. Nausea and vomiting were treated with injection ondansetron 4 mg IV. Motor block was assessed using the Modified Bromage score (Modified Bromage scale was Graded as 0 – No paralysis, able to flex hips/knees/ankles, 1 – able to move knees, unable to raise extended legs, 2 – able to flex ankles, unable to flex knees, and 3 – unable to move any part of limb–complete block), and time to achieve modified Bromage ≥2 was noted as the onset of motor block. The time to return to modified Bromage 0 was noted as the duration of motor block. Sensory block was assessed in dermatomal areas of T8 to S2 with a blunt 23G hypodermic needle using the following scaling system: 0 = normal sensation, 1 = loss of prick sensation (analgesia), and 2 = loss of touch sensation (anesthesia). The onset of sensory block was the time from intrathecal injection to the time taken to achieve T8 dermatomal level, and the duration of sensory block was the time taken by sensory block to regress up to S1 dermatome (in the heel) from the highest level achieved. The duration of analgesia was defined as the time from intrathecal injection to the time when the patient demanded for rescue analgesia. Postoperative pain was assessed using 10-point Visual Analog Scale (VAS) in which a score of “0” indicated “no pain” and a score of “10” indicated “most severe pain.” Whenever VAS ≥4, patients were administered injection diclofenac sodium 75 mg intramuscular as rescue analgesia and that time duration was considered as duration of analgesia.
Perioperative sedation was assessed using the Ramsay sedation score (RSS). RSS was graded as follows: 1 – patient is anxious and agitated or restless, or both; 2 – patient is co-operative, oriented, and tranquil; 3 – patient responds to commands only; 4 – patient exhibits brisk response to a light glabellar tap or loud auditory stimulus; 5 – patient exhibits a sluggish response to a light glabellar tap or loud auditory stimulus; and 6 – patient exhibits no response. Postoperatively, vital parameters including HR, SBP, DBP, MAP, SpO2, and RR were recorded. Side effects (nausea, vomiting, hypotension, bradycardia, and pruritus) were observed and recorded for every 2 h till 12 h.
Statistical analysis
Based on a previous study by Bidikar et al.,[6] the sample size was calculated to be 36 patients in each group at an alpha error of 0.05 and 80% power to detect an expected difference in duration of motor block to be 8.6 ± 13 min. The sample size was increased to 40 in each group after considering 10% dropouts. Although the duration of analgesia was the primary outcome measure, the sample size was calculated to be 1 in each group on the basis of the duration of analgesia. Based on the central limit theorem, a minimum of 30 subjects should be there in each group to obtain a significant difference in results, so we have calculated the sample size on the basis of all parameters, of which we chose the duration of motor block for the calculation of final sample size to increase the power and external validity of this study as described in statistical analysis.
The data analysis was performed using Epi Info version 7.2.1.0 statistical software (CDC Epi Info version 7.2.1.0 (US) statistical software). Data were presented as mean ± standard deviation, median, and range or number of patients. Categorical or nominal variables were expressed as number and percentage and analyzed using Chi-square test or Fischer's exact test as applicable. Student's t-test was used to analyze the parameters which are on a continuous scale between two groups. P < 0.05 was considered to be statistically significant.
ResultsThe demographic profile, baseline hemodynamic parameters, and duration of surgery were comparable between the two groups [Table 1]. The mean time of onset of sensory block (T8 dermatome) in Group Levobupivacaine (L) (5.6 ± 1.53 min) was longer as compared to Group Levobupivacaine + fentanyl (LF) (4.7 ± 1.70 min), and the difference was statistically significant (P = 0.015). The median highest level of sensory blockade achieved in Group L and Group LF was T8 and T6, respectively. The mean time to achieve Bromage 2 motor block was longer in Group L (9.25 ± 1.64 min) as compared to Group LF (7.45 ± 1.74 min), and the difference was highly significant (P < 0.001). The duration of sensory block was significantly prolonged in Group LF (268.88 ± 21.05 min) as compared to Group L (198 ± 17.81 min) (P < 0.001), but the duration of motor block was comparable between two groups (144.25 ± 13.82 min in Group L and 139.88 ± 31.83 min in Group LF) (P = 0.428) [Table 2].
Table 1: Demographic profile, duration of surgery, and baseline hemodynamic parameters in group levobupivacaine and group levobupivacaine + fentanyl
Table 2: Block characteristics in group levobupivacaine and group levobupivacaine + fentanylThe assessment of postoperative pain was done using the VAS score. The difference of VAS score was statistically significant from 0 h to 6 h (P < 0.05) and 10 h to 12 h (P < 0.05) [Table 3]. Patients demanded the first dose of rescue analgesia after approximately 4 h in Group L, but in Group LF, the demand for rescue analgesia was after approximately 6 h [Figure 2]. The duration of analgesia was significantly prolonged in Group LF (336.5 ± 31.3 min) as compared to Group L (223.65 ± 32.17 min) (P < 0.001). The total number of doses of rescue analgesia required in 24 h was also significantly lesser in Group LF as compared to Group L (P < 0.0001) [Table 2].
Figure 2: Line diagram showing mean VAS scores in Group L and Group LF. Mean VAS score at various time intervals. VAS started increasing in Group L and was >3 after 4 h and patient demanded first dose of rescue analgesia. In Group LF, VAS was >3 after 6 h and first dose of rescue analgesia was given. Group LF required less number of doses of rescue analgesia as compared to Group L. P < 0.0001. Group L: Levobupivacaine, Group LF: Levobupivacaine + fentanyl. VAS: Visual Analog ScaleOn intergroup comparison, the hemodynamic parameters (HR, SBP, DBP, MAP, RR, and SpO2) were comparable between two groups (P > 0.05). Among hemodynamic parameters, HR remained comparable from their baseline values in both the groups throughout the study. Two patients (5%) in Group LF and one patient (2.5%) in Group L (P = 1.00) had bradycardia intraoperatively that was managed using IV atropine. Hypotension was observed in 1 (2.5%) patient in Group L, but none of the patients in Group LF had hypotension. SBP, DBP, and MAP also remained comparable to their baseline values throughout the study [Figure 3]. None of the patients had respiratory depression in both the groups. None of the patients had any side effects such as nausea, vomiting, pruritus, sedation, headache, or backache in the postoperative period in both the groups.
Figure 3: Mean HR, SBP, DBP, mean arterial pressure, and SpO2 in Group L and Group LF intraoperatively. Mean HR, SBP, DBP, MAP, and SpO2 at various time intervals. Vitals remained stable and comparable at all intervals. Group L: Levobupivacaine, Group LF: Levobupivacaine + fentanyl. HR: Heart rate. SBP: Systolic blood pressure. DBP: Diastolic blood pressure. MAP: Mean arterial pressure. SpO2: Oxygen saturation Discussion The present study demonstrates that 25 μg fentanyl added to 12.5 mg intrathecal 0.5% levobupivacaine provides a longer duration of analgesia, which is more than that obtained from 12.5 mg of 0.5% levobupivacaine alone for infraumbilical surgeries. Apart from prolonged duration of analgesia, a faster onset of both sensory and motor block was noted along with an added advantage of shorter duration of motor block and reduced rescue analgesic consumption.
Postoperative pain is one of the most common distressing complaints of a patient. It amplifies the surgery-induced stress response, hinders early ambulation, and can prolong hospital stay. An effective anesthetic approach should focus on pain management during the postoperative period, thereby decreasing morbidity and patient discomfort.
Ever since the neurobiology of pain and pharmacology of available drugs have been understood, a breakthrough has occurred in the management of postoperative pain. Various intrathecal adjuvants of different groups have been used and evolved over a time with varying mechanisms of action. Opioids (morphine, fentanyl, sufentanil, hydromorphone, buprenorphine, and tramadol) have been used as adjuvants to local anesthetics with varying success.[7] Levobupivacaine, an amino-amide local anesthetic drug, was reported to have differential neuraxial blockade, i.e., faster onset and prolonged duration of sensory block with shorter duration of motor block and lower cardiac toxicity.[8] Fentanyl has a nociceptive action which acts on both μ1 and μ2 receptors at the dorsal horn of the spinal cord and potentiates afferent sensory blockade. Fentanyl, when used as an adjuvant, has a synergistic action with local anesthetics which improves the quality of intraoperative analgesia and anesthesia along with postoperative analgesia without any significant side effects.
In the present study, the onset of sensory block and time to achieve maximum sensory and motor block were significantly faster in Group LF compared to Group L. The duration of sensory block and postoperative analgesia was also significantly prolonged in levobupivacaine and fentanyl groups as compared to plain levobupivacaine group without prolonging the motor block. The maximum sensory level achieved in Group LF was T6, whereas it was T8 in Group L although the maximum motor block was Bromage 2 in both the groups. Postoperatively, the time to achieve VAS >3 was also prolonged in Group LF compared to Group L as well as the number of doses of rescue analgesics consumed in 24 h was also lesser in Group LF.
Bozdogan Ozyilkan et al.[9] compared levobupivacaine 0.5% 2.2 ± 0.2 ml, levobupivacaine 0.5% 2.2 ± 0.2 ml with 2.5 mg sufentanyl, and levobupivacaine 0.5% 2.2 ± 0.2 ml with fentanyl 10 μg and concluded that onset of sensory blockade was faster in sufentanyl and fentanyl group than control group. In this study, we found similar results in terms of mean time of onset of sensory block in the fentanyl group. The faster onset with fentanyl could be attributed to the synergistic effect of opioids with local anesthetic agents. The time of onset of motor block was also found to be faster in Group LF. The early onset of motor block in Group LF compared to Group L in this study might be due to the same reason, i.e., the synergistic effect of opioids with local anesthetics. The results of this study are comparable with those of Attri et al.[10] where they compared levobupivacaine 0.5% 10 mg and levobupivacaine 0.5% 10 mg with fentanyl 25 μg for infraumbilical surgeries and found that the onset of motor block was significantly faster in fentanyl group.
Agrawal et al.[11] compared levobupivacaine 15 mg + normal saline 0.5 ml with levobupivacaine 15 mg + fentanyl 25 μg and found that the duration of sensory block was prolonged in the fentanyl group. Similarly, Attri et al.[10] showed that the duration of sensory block was significantly longer in the fentanyl group as compared to the control group. The duration of sensory block was also significantly prolonged in this study too. Maniyar et al.[12] compared levobupivacaine 7.5 mg alone and levobupivacaine 5 mg with fentanyl 25 μg and found that the duration of motor block was comparable in both groups, which is similar to this study and also consistent with various other studies in the literature too.[13],[14],[15],[16] The prolonged motor block might be distressing in the postoperative period, so it did not seem to be a beneficial in terms of patient satisfaction.
Bidikar et al.[6] compared levobupivacaine 10 mg with levobupivacaine 7.5 mg + fentanyl 12.5 μg and found the total duration of analgesia in fentanyl group to be significantly longer than levobupivacaine alone group. Rajsekaran et al.[17] conducted a study on parturients where they compared levobupivacaine 10 mg + normal saline 0.3 ml with levobupivacaine 10 mg + fentanyl 15 μg and showed that the duration of analgesia in fentanyl group was significantly longer than levobupivacaine group. These results are similar to this study, and the longer duration of analgesia in this study could have been due to a higher dose of both local anesthetic as well as fentanyl. Attri et al.[10] also found similar results in terms of duration of analgesia. As far as hemodynamic parameters are concerned, this study findings are similar to the study done by Attri et al.[10] and Gadkari et al.[18] who showed no significant variation in hemodynamics.
This study revealed that VAS score was significantly lower in Group LF as compared to Group L. VAS scores were significantly different throughout the postoperative period. The total dose of rescue analgesic required postoperatively was also significantly lesser in Group LF as compared to Group L where most of the patients (37) required only 1 dose of rescue analgesic. In this study, hypotension was observed in 1 (2.5%) patient in Group L, but none of the patients in Group LF had hypotension. Bradycardia was observed in 1 (2.5%) patient in Group L and 2 (5%) patients in Group LF. There was no statistically significant difference in perioperative sedation and postoperative complications such as hypotension, bradycardia, pruritus, nausea, and vomiting between two groups. This study corroborates with the results of Bozdogan Ozyilkan et al.[9] and Koppal et al.[19]
In this study, we focused on the effects of fentanyl as an adjuvant to levobupivacaine administered intrathecally and evaluated its effect on the efficacy of subarachnoid block, but still, there are few limitations of this study. No premedication was used, so co-operation of the patient was needed, only a single dose of intrathecal fentanyl (25 μg) was compared as an adjuvant, and the drug dose remained fixed regardless of the patient's height and weight.
The clinical significance of reduced duration of motor block resulting from levobupivacaine plus fentanyl would be early ambulation. The pharmacological profile of levobupivacaine reveals very less cardiotoxicity. Further studies need to be conducted to evaluate and strengthen the role of different doses of fentanyl as an effective and safe adjuvant with isobaric levobupivacaine.
ConclusionWe concluded that intrathecal fentanyl (25 μg) can be effectively used as an adjuvant to isobaric 0.5% levobupivacaine, as it has significantly prolonged the duration of analgesia, with lesser rescue analgesic consumption along with faster onset of both sensory as well as motor block and stable hemodynamics without prolonging the motor block and minimal adverse effects in patients undergoing infraumbilical surgeries.
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Conflicts of interest
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